Cesarean delivery (CD) is the most frequently performed major surgical procedure in the industrialized world. Financial and medical considerations have generated pressures to reduce the rate of CD. We posit that the process of myometrial wound healing determines the future morphology, functional behavior and risk of rupture of the uterine scar. Therefore, optimizing myometrial healing after CD will optimize myometrial structural and functional integrity and minimize the risk of uterine scar rupture in a subsequent pregnancy. Previous studies showed that hematopoetic bone marrow stem cells play a crucial role in post-injury healing of the kidney, ligaments and cardiac muscle. We postulate that hematopoetic bone marrow stem cells also participate in the repair of the uterine incision post-CD. We will test this hypothesis in three specific aims using two strains of mice that differ dramatically in their underlying wound healing characteristics. C57BL/6 mice heal predominantly by fibrotic repair while MRL/MPJ heal by regeneration. The first two aims will evaluate the structural and functional aspects of uterine healing while the third aim addresses the role played by hematopoetic stem cells in repair of the uterine incision. We propose to: (1) investigate molecular and structural aspects of uterine wound healing in MRL/MpJ+/+; C57BL/6 ; C57BL/6-Tg(UBC-GFP)30Scha and B6.MRL-Tnfrsf6lpr mice; (2) investigate how uterine scarring alters myometrial function; and (3) investigate the role of stem cells in uterine regeneration/repair using chimeric mice by transplanting bone marrow stem cells from mice expressing ubiquitous green fluorescent protein into C57BL/6 and MRL congenic mice for the same haplotype. The studies outlined in this proposal are likely to open new and promising areas for understanding the mechanisms of uterine healing and thus for identifying strategies for enhancing the integrity of the uterine scar and ultimately for prevention of uterine rupture during trials of labor after prior CD.